The invention relates generally to the field of magnetic resonance (MR) imaging using paramagnetic nanoparticles. In particular, the present invention is directed to chelator-functionalized nanoparticles, which may be used as T1 MR agents. Also provided herein are methods of making and methods of using chelator-functionalized nanoparticles.
Conventional clinical MR imaging contrast agents are small molecule based extracellular fluid agents that are used to provide broad anatomical contrast. However they are not optimal for the molecular imaging of oncology and cardiovascular diseases because of their short blood residence time and low signal per molecule.
Nanoparticle-based probes have shown great potential for bioimaging, diagnostic, and therapeutic purposes. Various nanoparticle-based MR imaging contrast agents have been investigated, including liposomes, micelles, vesicles, polymers, and proteins labeled with paramagnetic metal ions.
Although the T1 imaging mode is the preferred method of radiologists, there is no T1 nanoparticle composition currently available clinically. Furthermore, many nanoparticles suffer from poor stability due to aggregation. Size variation resulting from particle aggregation adversely affects the pharmacokinetic properties of the nanoparticle agents including variable distribution and poor elimination kinetics.